CN110938044B - 一种硒氰基化试剂、其制备及应用 - Google Patents
一种硒氰基化试剂、其制备及应用 Download PDFInfo
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Abstract
本发明涉及一种硒氰基化试剂、其制备及应用,属于硒氰基化合物制备技术领域。本发明所述硒氰基化试剂为氮‑硒氰基糖精,属于阳离子型硒氰基化试剂,使用时相对安全,毒害性小,反应活性高,不但可以以高收率合成含硒氰基化合物,同时在催化剂催化作用下,还可以合成具有高立体选择性的手性含硒氰基化合物。
Description
技术领域
本发明涉及一种硒氰基化试剂、其制备及应用,属于硒氰基化合物制备技术领域。
背景技术
硒元素是人体的必须微量元素之一,在人体内主要以硒蛋白的形式存在。医学研究证明,肝病、白内障、肌肉萎缩、心肌坏死以及免疫力下降等诸多疾病与人体缺硒有关。含硒化合物作为生物活性分子,在抗氧化、抗癌等方面有着优异的表现。含硒氰基化合物同样作为抗癌、抗氧化活性生物分子被人们广泛关注。另外,氰基在有机合成领域是一个重要的中间体,可以转化成其他官能团,而含硒氰基化合物可以转化成其他含硒化合物,因此将硒氰基引入有机小分子中能够产生非常重要的作用。
对于小分子中引入硒氰基(SeCN)的方法主要分为:直接引入法和间接引入法。间接引入法主要是通过采用氰基试剂氰化硒醇的方法,在硒原子上引入氰基来构建硒氰基官能团。直接引入法又可以分为两类:一种方法是采用阴离子型硒氰基化试剂如硒氰酸钾,同时底物必须带有离去基团,才能发生亲核取代反应,引入硒氰基,这样便对底物结构要求较高,必须提前引入离去基团;以及采用硒氰酸钾与氧化剂体系,这种方法虽说可以直接在碳原子上引入硒氰基,但是额外加入的氧化剂有可能对底物分子产生其他副反应,同时一些反应中会用到过渡金属,如果是在药物后期修饰中用到过渡金属,由于过渡金属毒性较大,且除去过渡金属也会加大成本。另一种方法是采用阳离子型硒氰基化试剂,虽然说使用该类试剂无需要求底物分子提前引入离去基团,或者加入氧化剂,但是目前所采用的阳离子型硒氰基化试剂如(SeCN)2和Se(SeCN)2在反应中都容易生成剧毒的硒氰酸,后者可以进一步分解成氢氰酸,对人体和环境损害很大。因此,寻求反应条件温和、转化率高的进入硒氰基的方法是目前急需解决的问题。
发明内容
针对现有技术中存在的不足,本发明提供一种硒氰基化试剂、其制备及应用,该试剂是一种基于糖精骨架的全新的硒氰基化试剂,该试剂制备方法简单,而且能与β-酮酯类化合物进行反应得到含有硒氰基的化合物且反应条件温和、转化率高。
本发明的目的是通过以下技术方案实现的。
一种硒氰基化试剂,所述硒氰基化试剂为氮-硒氰基糖精,其结构式如下所示:
本发明所述硒氰基化试剂的制备步骤如下:氮-卤代糖精与硒氰酸银在有机溶剂Ⅰ中发生氧化还原反应生成氮-硒氰基糖精,具体的合成路线如下所示:
其中,X为Cl或Br;所用有机溶剂Ⅰ不与氮-卤代糖精以及硒氰酸银发生反应即可,有机溶剂Ⅰ优选腈类溶剂或卤代烃类溶剂,腈类溶剂优选乙腈,卤代烃类溶剂优选二氯甲烷或三氯甲烷;有机溶剂Ⅰ与氮-卤代糖精的体积质量比优选1mL/g~100mL/g,更优选1mL/g~50mL/g;硒氰酸银与氮-卤代糖精的摩尔比优选1~5:1,更优选1~2:1。
本发明所述硒氰基化试剂的应用,氮-硒氰基糖精与β-酮酯类化合物Ⅰ在有机溶剂Ⅱ中发生取代反应生成含硒氰基化合物;
或者,
在催化剂的作用下以及-100℃~10℃的温度下,氮-硒氰基糖精与β-酮酯类化合物Ⅱ在有机溶剂Ⅲ中发生取代反应生成具有手性的含硒氰基化合物;
其中,β-酮酯类化合物Ⅰ的结构式为含硒氰基化合物的结构式为n=0、1或2;β-酮酯类化合物Ⅱ的结构式为具有手性的含硒氰基化合物的结构式为R1为氢、卤素、芳基(包含取代以及未取代的芳基,如苯基、萘基、四氢萘基、联苯基等)、烷氧基(包含取代以及未取代的烷氧基,如烯丙基烷氧基、苄基烷氧基等)或烷基;R2为烷基(包含取代以及为取代的烷基,如甲基、叔丁基、金刚烷基等);有机溶剂Ⅱ不与氮-硒氰基糖精以及β-酮酯类化合物Ⅰ反应即可,优选卤代烃类溶剂、腈类溶剂或醚类溶剂,卤代烃类溶剂优选二氯甲烷或三氯甲烷,腈类溶剂优选乙腈,醚类溶剂优选乙醚、四氢呋喃;氮-硒氰基糖精在有机溶剂Ⅱ以及有机溶剂Ⅲ中的浓度优选1mg/mL~50mg/mL,更优选10mg/mL~30mg/mL;氮-硒氰基糖精与β-酮酯类化合物Ⅰ以及β-酮酯类化合物Ⅱ的摩尔比为1~3:1,更优选1~1.3:1;有机溶剂Ⅲ不与氮-硒氰基糖精、β-酮酯类化合物以及催化剂反应即可,优选腈类溶剂或卤代烃类溶剂,腈类溶剂优选乙腈,氯代烃类溶剂优选二氯甲烷或三氯甲烷;催化剂是由路易斯酸和手性氮配体组成的复配催化剂,所述的路易斯酸优选金属路易斯酸,所述的金属路易斯酸优选镍盐或铜盐,更优选三氟甲磺酸镍或三氟甲磺酸酮,所述的手性氮配体优选手性噁唑啉配体,所述的手性噁唑啉配体优选手性双噁唑啉配体,更优选手性二苯并呋喃双噁唑啉配体,所述的路易斯酸与β-酮酯类化合物Ⅱ的摩尔比值为0.1~1.0:1,进一步优选0.1~0.2:1,所述的手性氮配体与β-酮酯类化合物Ⅱ的摩尔比值为0.1~1.0:1,进一步优选0.1~0.2:1;制备具有手性的含硒氰基化合物的反应温度优选-40℃~-80℃。
进一步地,β-酮酯类化合物的具体结构如下,其中β-酮酯类化合物Ⅰ中n=1时与β-酮酯类化合物Ⅱ的结构相同;
有益效果:
本发明所述的硒氰基化试剂属于阳离子型硒氰基化试剂,使用时相对安全,毒害性小,反应活性高,不但可以以高收率合成含硒氰基化合物,同时在催化剂催化作用下,还可以合成具有高立体选择性的手性含硒氰基化合物。
附图说明
图1为实施例1制备的氮-硒氰基糖精的氢谱图。
图2为实施例1制备的氮-硒氰基糖精的碳谱谱图。
图3为实施例5制备的含硒氰基化合物的氢谱图。
图4为实施例5制备的含硒氰基化合物的碳谱图。
图5为实施例13制备的含硒氰基化合物的氢谱图。
图6为实施例13制备的含硒氰基化合物的碳谱图。
图7为实施例16制备的含硒氰基化合物的高效液相色谱图。
具体实施方式
下面结合具体实施方式对本发明作进一步阐述,其中,所述方法如无特别说明均为常规方法,所述原材料如无特别说明均能从公开商业途径而得或根据文献制备而得。
实施例1
硒氰基化试剂氮-硒氰基糖精的具体制备步骤如下:
氮-氯代糖精(2.17g)与硒氰酸银(2.24g)在乙腈(35mL)中室温(10℃~35℃,下同)下反应1h,先用硅藻土过滤再通过减压旋转蒸发除去溶剂,得到浅黄色固体氮-硒氰基糖精(2.45g,产率85%),具体合成路线如下所示:
本实施例所制备的氮-硒氰基糖精的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp(熔点):225–227℃;1H NMR(400MHz,CDCl3)δ:8.06(d,J=7.2Hz,1H,Ar–H),7.93–7.91(m,2H,Ar–H),7.89–7.84(m,1H,Ar–H),如图1所示;13C{1H}NMR(100MHz,CDCl3)δ:159.7,139.4,135.4,134.4,127.3,125.5,121.2,90.3(SeCN)ppm,如图2所示;IR(KBr):2151(SeCN),1712,1589,1572cm–1;HRMS(ESI):计算值C7H4NO3S for[M–SeCN]–181.9917,实验值181.9906。
实施例2
空气条件下将β-四氢萘酮金刚烷酯(16mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-β-四氢萘酮金刚烷酯(20mg,产率93%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:109–111℃;1H NMR(400MHz,CDCl3)δ:8.00(dd,J=7.6,1.2Hz,1H,Ar–H),7.58(dt,J=7.7,1.2Hz,1H,Ar–H),7.36(t,J=7.6Hz,1H,Ar–H),7.27(d,J=8.8Hz,1H,Ar–H),3.22–3.04(m,3H,CH2),2.75–2.68(m,1H,CH2),2.15(s,3H,Ad–H),2.07(s,6H,Ad–H),1.62(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:192.0,166.1,143.1,134.9,130.4,128.9,128.0,127.4,102.4(SeCN),85.0,65.6,40.8,35.9,35.2,30.8,28.1ppm;IR(KBr):2912,2852,2154(SeCN),1718,1680cm–1;HRMS(ESI)m/z计算值C22H23NNaO3Se for[M+Na]+452.0735,实验值452.0737。
实施例3
空气条件下将7-氯-β-四氢萘酮金刚烷酯(18mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-7-氯-β-四氢萘酮金刚烷酯(19mg,产率81%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-7-氯-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:142–144℃;1H NMR(400MHz,CDCl3)δ:7.96(d,J=2.4Hz,1H,Ar–H),7.51(dd,J=8.4,2.4Hz,1H,Ar–H),7.23(d,J=8.4Hz,1H,Ar–H),3.21–3.01(m,3H,CH2),2.73–2.66(m,1H,CH2),2.16(s,3H,Ad–H),2.08(s,6H,Ad–H),1.63(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:190.9,165.8,141.3,134.8,133.7,131.6,130.5,127.6,102.0(SeCN),85.4,65.0,40.8,35.8,35.0,30.9,27.5ppm;IR(KBr):2912,2852,2154(SeCN),1716,1683,1595cm–1;HRMS(ESI)m/z计算值C22H26ClN2O3Se for[M+NH4]+481.0792,实验值481.0784。
实施例4
空气条件下将7-甲基-β-四氢萘酮金刚烷酯(17mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-7-甲基-β-四氢萘酮金刚烷酯(18mg,产率83%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-7-甲基-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:152–154℃;1H NMR(400MHz,CDCl3)δ:7.80(s,1H,Ar–H),7.37(dd,J=8.0,1.2Hz,1H,Ar–H),7.16(d,J=8.0Hz,1H,Ar–H),3.20–2.99(m,3H,CH2),2.73–2.67(m,1H,CH2),2.37(s,3H,CH3),2.16(s,3H,Ad–H),2.09(s,6H,Ad–H),1.63(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:192.2,166.3,140.3,137.3,136.0,130.2,128.8,128.0,102.5(SeCN),84.9,65.9,40.8,35.9,35.3,30.9,27.7,20.9ppm;IR(KBr):2912,2853,2154(SeCN),1718,1676cm–1;HRMS(ESI)m/z计算值C23H29N2O3Se for[M+NH4]+461.1338,实验值461.1331。
实施例5
空气条件下将7-(2-萘基)-β-四氢萘酮金刚烷酯(23mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-7-(2-萘基)-β-四氢萘酮金刚烷酯(16mg,产率59%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-7-(2-萘基)-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:180–182℃;1H NMR(400MHz,CDCl3)δ:8.37(s,1H,Ar–H),8.07(s,1H,Ar–H),7.95–7.87(m,4H,Ar–H),7.74(d,J=8.4Hz,1H,Ar–H),7.53=7.52(m,2H,Ar–H),7.40(d,J=8.4Hz,1H,Ar–H),3.26–3.10(m,3H,CH2),2.80–2.73(m,1H,CH2),2.17(s,3H,Ad–H),2.12(s,6H,Ad–H),1.63(s,6H,Ad–H),如图3所示;13C{1H}NMR(100MHz,CDCl3)δ:192.1,166.2,142.0,140.4,136.5,133.7,133.5,132.8,130.8,129.6,128.7,128.2,127.6,126.5,126.4,126.4,125.9,124.9,102.3(SeCN),85.1,65.7,40.8,35.9,35.2,30.9,27.8ppm,如图4所示;IR(KBr):2912,2852,2154(SeCN),1716,1689cm–1;HRMS(ESI)m/z计算值C32H33N2O3Se for[M+NH4]+573.1651,实验值573.1638。
实施例6
空气条件下将7-甲氧基-β-四氢萘酮金刚烷酯(18mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-7-甲氧基-β-四氢萘酮金刚烷酯(22mg,产率96%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-7-甲氧基-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:129–131℃;1H NMR(400MHz,CDCl3)δ:7.44(d,J=2.4Hz,1H,Ar–H),7.19–7.12(m,2H,Ar–H),3.84(s,3H,OCH3),3.20–2.97(m,3H,CH2),2.74–2.66(m,1H,CH2),2.16(s,3H,Ad–H),2.09(s,6H,Ad–H),1.63(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:192.0,166.2,158.7,135.8,131.1,130.1,123.5,109.6,102.4(SeCN),85.0,55.6,40.8,35.9,35.5,30.9,27.3ppm;IR(KBr):2912,2852,2154(SeCN),1716,1684cm–1;HRMS(ESI)m/z计算值C23H26NO4Se for[M+H]+460.1022,实验值460.1016。
实施例7
空气条件下将7-(3,5-二溴苄氧基)-β-四氢萘酮金刚烷酯(29mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-7-(3,5-二溴苄氧基)-β-四氢萘酮金刚烷酯(27mg,产率78%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-7-(3,5-二溴苄氧基)-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:63–65℃;1H NMR(400MHz,CDCl3)δ:7.63(s,1H,Ar–H),5.51(d,J=1.6Hz,2H,Ar–H),7.48(d,J=1.6Hz,1H,Ar–H),7.21–7.20(m,2H,Ar–H),5.02(s,2H,OCH2),3.21–2.98(m,3H,CH2),2.74–2.67(m,1H,CH2),2.16(s,3H,Ad–H),2.08(s,6H,Ad–H),1.63(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:191.8,166.1,157.2,140.2,136.6,133.7,131.2,130.5,128.9,123.9,123.2,110.7,102.3(SeCN),85.1,68.5,65.5,40.8,35.9,35.4,30.9,27.3ppm;IR(KBr):2912,2852,2154(SeCN),1718,1676,1558cm–1;HRMS(ESI)m/z计算值C29H31Br2N2O4Se for[M+NH4]+710.9790,实验值710.9774。
实施例8
空气条件下将7-(2,4,5-三氟苄氧基)-β-四氢萘酮金刚烷酯(24mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-7-(2,4,5-三氟苄氧基)-β-四氢萘酮金刚烷酯(22mg,产率74%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-7-(2,4,5-三氟苄氧基)-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、核磁共振氟谱、红外光谱以及高分辨质谱的表征结果如下:mp:177–179℃;1H NMR(400MHz,CDCl3)δ:7.52(d,J=2.0Hz,1H,Ar–H),7.36–7.30(m,1H,Ar–H),7.21–7.18(m,2H,Ar–H),7.01–6.95(m,1H,Ar–H),5.08(s,2H,OCH2),3.21–3.03(m,3H,CH2),2.74–2.67(m,1H,CH2),2.16(s,3H,Ad–H),2.09(s,6H,Ad–H),1.63(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:191.8,166.1,157.2,136.6,131.6,130.4,123.8,117.4,117.4,117.2,117.2,110.7,105.9,105.7,105.7,105.4,102.3(SeCN),85.1,65.5,63.0,62.9,40.8,35.9,35.4,30.9,27.3ppm;19F{1H}NMR(376MHz,CDCl3)δ:–119.8(dd,4JF-F=15.4,5JF-F=3.8Hz),–133.3(dd,3JF-F=21.4,5JF-F=4.1Hz),–142.0(dd,3JF-F=21.4,4JF-F=15.4Hz);IR(KBr):2914,2854,2154(SeCN),1718,1680,1520cm–1;HRMS(ESI)m/z计算值C29H30F3N2O4Sefor[M+NH4]+607.1317,实验值607.1318。
实施例9
空气条件下将6-(4-甲基苄氧基)-β-四氢萘酮金刚烷酯(22mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-6-(4-甲基苄氧基)-β-四氢萘酮金刚烷酯(27mg,产率98%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-6-(4-甲基苄氧基)-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下;1H NMR(400MHz,CDCl3)δ:7.97(d,J=8.8Hz,1H,Ar–H),7.30(d,J=8.0Hz,2H,Ar–H),7.21(d,J=8.0Hz,2H,Ar–H),6.93(dd,J=8.8,2.4Hz,1H,Ar–H),6.77(d,J=2.4Hz,1H,Ar–H),5.08(s,2H,OCH2),3.18–2.96(m,3H,CH2),2.72–2.65(m,1H,CH2),2.37(s,3H,CH3),2.16(s,3H,Ad–H),2.10(s,6H,Ad–H),1.63(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:190.3,166.3,164.0,145.9,138.3,132.6,130.7,129.4,127.6,123.8,114.8,113.6,102.7(SeCN),84.8,70.2,65.6,40.8,35.9,35.3,30.8,28.5,21.2ppm;IR(KBr):2912,2852,2152(SeCN),1720,1666,1597cm–1;HRMS(ESI)m/z计算值C30H31NNaO4Se for[M+Na]+572.1311,实验值572.1318。
实施例10
空气条件下将6-烯丙氧基-β-四氢萘酮金刚烷酯(19mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-6-烯丙氧基-β-四氢萘酮金刚烷酯(24mg,产率99%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-6-烯丙氧基-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:128–130℃;1H NMR(400MHz,CDCl3)δ:7.97(d,J=8.8Hz,1H,Ar–H),6.88(dd,J=8.8,2.4Hz,1H,Ar–H),6.71(d,J=2.4Hz,1H,Ar–H),6.08–5.98(m,1H,CH2CH),5.42(dd,J=17.2,1.2Hz,1H,CH2CH),5.33(dd,J=10.4,1.2Hz,1H,CH2CH),4.63(d,J=5.2Hz,2H,OCH2),3.18–2.97(m,3H,CH2),2.72–2.65(m,1H,CH2),2.16(s,3H,Ad–H),2.10(s,6H,Ad–H),1.63(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:190.3,166.3,163.8,145.8,132.0,130.6,123.8,118.4,114.7,113.5,102.7(SeCN),84.8,69.0,65.6,40.8,35.9,35.2,30.8,28.5ppm;IR(KBr):2920,2850,2156(SeCN),1716,1668,1602,1556cm–1;HRMS(ESI)m/z计算值C25H28NO4Se for[M+H]+486.1178,实验值486.1183。
实施例11
空气条件下将5-甲氧基-β-四氢萘酮金刚烷酯(18mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-5-甲氧基-β-四氢萘酮金刚烷酯(22mg,产率96%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-5-甲氧基-β-四氢萘酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:135–137℃;1H NMR(400MHz,CDCl3)δ:7.60(d,J=8.0Hz,1H,Ar–H),7.32(t,J=8.0Hz,1H,Ar–H),7.08(d,J=8.0Hz,1H,Ar–H),3.88(s,3H,CH3),3.25–3.18(m,2H,CH2),2.86–2.77(m,1H,CH2),2.64(dt,J=12.8,4.8Hz,1H,CH2),2.15(s,3H,Ad–H),2.08(s,6H,Ad–H),1.62(s,6H,Ad–H);13C{1H}NMR(100MHz,CDCl3)δ:192.3,166.1,156.7,132.2,131.3,127.8,119.4,102.4(SeCN),84.9,65.8,55.7,40.8,35.9,34.4,30.9,22.3ppm;IR(KBr):2912,2852,2154(SeCN),1716,1683cm–1;HRMS(ESI)m/z计算值C23H29N2O4Se for[M+NH4]+477.1287,实验值477.1280。
实施例12
空气条件下将β-四氢萘酮异丁酯(13mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-β-四氢萘酮异丁酯(14mg,产率80%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-β-四氢萘酮异丁酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:1H NMR(400MHz,CDCl3)δ:8.02(d,J=8.0Hz,1H,Ar–H),7.57(t,J=7.6Hz,1H,Ar–H),7.37(t,J=7.6Hz,1H,Ar–H),7.27(d,J=7.6Hz,1H,Ar–H),4.03–3.94(m,2H,CO2CH2),3.30–3.04(m,3H,CH2),2.79–2.72(m,1H,CH2),1.95–1.85(m,1H,CH),0.81(dd,J=6.8,3.2Hz,6H,CH3);13C{1H}NMR(100MHz,CDCl3)δ:191.6,167.3,143.2,135.1,130.2,129.0,128.2,127.4,101.9(SeCN),72.9,64.4,34.9,27.9,27.6,18.7ppm;IR(KBr):2962,2927,2154(SeCN),1728,1678,1629,1598cm–1;HRMS(ESI)m/z计算值C16H18NO3Se for[M+H]+352.0446,实验值352.0442。
实施例13
空气条件下将β-二氢茚酮金刚烷酯(16mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol)溶于二氯甲烷(1.0mL),室温下搅拌反应12h后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到2-硒氰基-β-二氢茚酮金刚烷酯(18mg,产率87%),其纯度经氢谱鉴定大于95%。
本实施例所制备的2-硒氰基-β-二氢茚酮金刚烷酯的核磁共振氢谱、核磁共振碳谱、红外光谱以及高分辨质谱的表征结果如下:mp:107–109℃;1H NMR(400MHz,CDCl3)δ:7.87(d,J=8.0Hz,1H,Ar–H),7.71(t,J=7.6Hz,1H,Ar–H),7.52–7.46(m,2H,Ar–H),4.14(d,Jab=18.4Hz,1H,CH2),3.79(d,Jab=18.4Hz,1H,CH2),2.17(s,3H,Ad–H),2.06(s,6H,Ad–H),1.63(s,6H,Ad–H),如图5所示;13C{1H}NMR(100MHz,CDCl3)δ:196.5,165.9,151.2,136.6,133.1,128.6,126.0,125.7,101.3(SeCN),86.3,62.8,41.0,40.9,35.8,30.9ppm,如图6所示;IR(KBr):2912,2852(SeCN),2152,1722,1604,1589cm–1;HRMS(ESI)m/z计算值C21H22NO3Se for[M+H]+416.0759,实验值416.0756。
实施例14
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入β-四氢萘酮金刚烷酯(16mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-β-四氢萘酮金刚烷酯(20mg,产率93%,92%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:109–111℃。1H NMR(400MHz,CDCl3)δ:8.00(dd,J=7.6,1.2Hz,1H,Ar–H),7.58(dt,J=7.7,1.2Hz,1H,Ar–H),7.36(t,J=7.6Hz,1H,Ar–H),7.27(d,J=8.8Hz,1H,Ar–H),3.22–3.04(m,3H,CH2),2.75–2.68(m,1H,CH2),2.15(s,3H,Ad–H),2.07(s,6H,Ad–H),1.62(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:192.0,166.1,143.1,134.9,130.4,128.9,128.0,127.4,102.4(SeCN),85.0,65.6,40.8,35.9,35.2,30.8,28.1ppm。IR(KBr):2912,2852,2154(SeCN),1718,1680cm–1。HRMS(ESI)m/z计算值C22H23NNaO3Se for[M+Na]+452.0735,实验值452.0737。旋光值:[α]25 D=–49.1(c 0.70,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tR(次峰)=7.5min,tS(主峰)=8.4min。
实施例15
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入7-氯-β-四氢萘酮金刚烷酯(18mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-7-氯-β-四氢萘酮金刚烷酯(19mg,产率81%,70%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-7-氯-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:142–144℃。1H NMR(400MHz,CDCl3)δ:7.96(d,J=2.4Hz,1H,Ar–H),7.51(dd,J=8.4,2.4Hz,1H,Ar–H),7.23(d,J=8.4Hz,1H,Ar–H),3.21–3.01(m,3H,CH2),2.73–2.66(m,1H,CH2),2.16(s,3H,Ad–H),2.08(s,6H,Ad–H),1.63(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:190.9,165.8,141.3,134.8,133.7,131.6,130.5,127.6,102.0(SeCN),85.4,65.0,40.8,35.8,35.0,30.9,27.5ppm.IR(KBr):2912,2852,2154(SeCN),1716,1683,1595cm–1。HRMS(ESI)m/z计算值C22H26ClN2O3Se for[M+NH4]+481.0792,实验值481.0784。旋光值:[α]25 D=–33.9(c 0.40,CH2Cl2)。高效液相色谱(HPLC):AD-H柱(正己烷/异丙醇90:10,v/v,1.0mLmin–1,254nm),tR(次峰)=7.4min,tS(主峰)=8.3min。
实施例16
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入7-甲基-β-四氢萘酮金刚烷酯(17mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-7-甲基-β-四氢萘酮金刚烷酯(18mg,产率83%,91%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-7-甲基-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:152–154℃。1H NMR(400MHz,CDCl3)δ:7.80(s,1H,Ar–H),7.37(dd,J=8.0,1.2Hz,1H,Ar–H),7.16(d,J=8.0Hz,1H,Ar–H),3.20–2.99(m,3H,CH2),2.73–2.67(m,1H,CH2),2.37(s,3H,CH3),2.16(s,3H,Ad–H),2.09(s,6H,Ad–H),1.63(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:192.2,166.3,140.3,137.3,136.0,130.2,128.8,128.0,102.5(SeCN),84.9,65.9,40.8,35.9,35.3,30.9,27.7,20.9ppm.IR(KBr):2912,2853,2154(SeCN),1718,1676cm–1。HRMS(ESI)m/z计算值C23H29N2O3Se for[M+NH4]+461.1338,实验值461.1331。旋光值:[α]25 D=–63.3(c 0.84,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tR(次峰)=6.9min,tS(主峰)=7.5min,如图7所示。
实施例17
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入7-(2-萘基)-β-四氢萘酮金刚烷酯(23mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-7-(2-萘基)-β-四氢萘酮金刚烷酯(16mg,产率59%,83%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-7-(2-萘基)-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:180–182℃。1H NMR(400MHz,CDCl3)δ:8.37(s,1H,Ar–H),8.07(s,1H,Ar–H),7.95–7.87(m,4H,Ar–H),7.74(d,J=8.4Hz,1H,Ar–H),7.53=7.52(m,2H,Ar–H),7.40(d,J=8.4Hz,1H,Ar–H),3.26–3.10(m,3H,CH2),2.80–2.73(m,1H,CH2),2.17(s,3H,Ad–H),2.12(s,6H,Ad–H),1.63(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:192.1,166.2,142.0,140.4,136.5,133.7,133.5,132.8,130.8,129.6,128.7,128.2,127.6,126.5,126.4,126.4,125.9,124.9,102.3(SeCN),85.1,65.7,40.8,35.9,35.2,30.9,27.8ppm。IR(KBr):2912,2852,2154(SeCN),1716,1689cm–1。HRMS(ESI)m/z计算值C32H33N2O3Se for[M+NH4]+573.1651,实验值573.1638。旋光值:[α]25 D=–36.0(c 0.46,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇95:5,v/v,1.0mL min–1,254nm),tS(主峰)=24.1min,tR(次峰)=27.2min。
实施例18
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入7-溴-β-四氢萘酮金刚烷酯(20mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-7-溴-β-四氢萘酮金刚烷酯(23mg,产率91%,87%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-7-溴-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:149–151℃。1H NMR(400MHz,CDCl3)δ:8.12(d,J=2.4Hz,1H,Ar–H),7.66(dd,J=8.0,2.4Hz,1H,Ar–H),7.17(d,J=8.0Hz,1H,Ar–H),3.22–2.99(m,3H,CH2),2.73–2.65(m,1H,CH2),2.17(s,3H,Ad–H),2.08(s,6H,Ad–H),1.63(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:190.8,165.8,141.8,137.7,131.8,130.7,130.7,121.4,102.0(SeCN),85.4,65.0,40.8,35.8,34.9,30.9,27.6ppm.IR(KBr):2912,2851,2154(SeCN),1716,1684cm–1。HRMS(ESI)m/z计算值C22H26BrN2O3Se for[M+NH4]+525.0287,实验值525.0281。旋光值:[α]25 D=–48.7(c0.76,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tR(次峰)=8.7min,tS(主峰)=9.4min。
实施例19
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入5-甲氧基-β-四氢萘酮金刚烷酯(18mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-5-甲氧基-β-四氢萘酮金刚烷酯(22mg,产率96%,82%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-5-甲氧基-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:135–137℃。1H NMR(400MHz,CDCl3)δ:7.60(d,J=8.0Hz,1H,Ar–H),7.32(t,J=8.0Hz,1H,Ar–H),7.08(d,J=8.0Hz,1H,Ar–H),3.88(s,3H,CH3),3.25–3.18(m,2H,CH2),2.86–2.77(m,1H,CH2),2.64(dt,J=12.8,4.8Hz,1H,CH2),2.15(s,3H,Ad–H),2.08(s,6H,Ad–H),1.62(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:192.3,166.1,156.7,132.2,131.3,127.8,119.4,102.4(SeCN),84.9,65.8,55.7,40.8,35.9,34.4,30.9,22.3ppm.IR(KBr):2912,2852,2154(SeCN),1716,1683cm–1。HRMS(ESI)m/z计算值C23H29N2O4Se for[M+NH4]+477.1287,实验值477.1280。旋光值:[α]25 D=–29.3(c 0.30,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇98:2,v/v,1.0mL min–1,254nm),tR(次峰)=17.3min,tS(主峰)=19.0min。
实施例20
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入7-(3,5-二溴苄氧基)-β-四氢萘酮金刚烷酯(29mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-7-(3,5-二溴苄氧基)-β-四氢萘酮金刚烷酯(27mg,产率78%,70%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-7-(3,5-二溴苄氧基)-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:63–65℃。1H NMR(400MHz,CDCl3)δ:7.63(s,1H,Ar–H),5.51(d,J=1.6Hz,2H,Ar–H),7.48(d,J=1.6Hz,1H,Ar–H),7.21–7.20(m,2H,Ar–H),5.02(s,2H,OCH2),3.21–2.98(m,3H,CH2),2.74–2.67(m,1H,CH2),2.16(s,3H,Ad–H),2.08(s,6H,Ad–H),1.63(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:191.8,166.1,157.2,140.2,136.6,133.7,131.2,130.5,128.9,123.9,123.2,110.7,102.3(SeCN),85.1,68.5,65.5,40.8,35.9,35.4,30.9,27.3ppm。IR(KBr):2912,2852,2154(SeCN),1718,1676,1558cm–1。HRMS(ESI)m/z计算值C29H31Br2N2O4Se for[M+NH4]+710.9790,实验值710.9774。旋光值:[α]25 D=–31.2(c1.04,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tS(主峰)=16.1min,tR(次峰)=18.2min。
实施例21
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入6-(2,4,5-三氟苄氧基)-β-四氢萘酮金刚烷酯(24mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-6-(2,4,5-三氟苄氧基)-β-四氢萘酮金刚烷酯(27mg,产率91%,72%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-6-(2,4,5-三氟苄氧基)-β-四氢萘酮金刚烷酯的相关表征结果如下:mp:102–104℃。1H NMR(400MHz,CDCl3)δ:8.01(d,J=8.8Hz,1H,Ar–H),7.35–7.29(m,1H,Ar–H),7.03–6.96(m,1H,Ar–H),6.94(dd,J=8.8,2.8Hz,1H,Ar–H),6.78(d,J=2.8Hz,1H,Ar–H),5.12(s,2H,OCH2),3.19–2.99(m,3H,CH2),2.73–2.66(m,1H,CH2),2.16(s,3H,Ad–H),2.10(s,6H,Ad–H),1.63(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:190.3,166.3,163.0,146.0,130.8,124.5,119.6,119.5,119.5,119.5,119.4,119.4,119.3,119.3,117.5,117.5,117.4,117.4,117.3,117.3,117.2,117.2,114.5,113.5,106.0,105.8,105.7,105.5,102.6(SeCN),84.9,65.5,62.9,62.9,40.8,35.9,35.2,30.9,28.5ppm。19F{1H}NMR(376MHz,CDCl3)δ:–119.8(dd,4JF-F=15.4,5JF-F=4.1Hz),–132.7(dd,3JF-F=21.0,5JF-F=4.1Hz),–141.6(dd,3JF-F=21.0,4JF-F=15.4Hz)。IR(KBr):2914,1854,2154(SeCN),1718,1670,1597,1521cm–1。HRMS(ESI)m/z计算值C29H27F3NO4Se for[M+H]+590.1052,实验值590.1052。旋光值:[α]25 D=–7.0(c0.55,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tR(次峰)=17.0min,tS(主峰)=21.9min。
实施例22
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入6-(4-甲基苄氧基)-β-四氢萘酮金刚烷酯(22mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-6-(4-甲基苄氧基)-β-四氢萘酮金刚烷酯(27mg,产率98%,70%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-6-(4-甲基苄氧基)-β-四氢萘酮金刚烷酯的相关表征结果如下:1H NMR(400MHz,CDCl3)δ:7.97(d,J=8.8Hz,1H,Ar–H),7.30(d,J=8.0Hz,2H,Ar–H),7.21(d,J=8.0Hz,2H,Ar–H),6.93(dd,J=8.8,2.4Hz,1H,Ar–H),6.77(d,J=2.4Hz,1H,Ar–H),5.08(s,2H,OCH2),3.18–2.96(m,3H,CH2),2.72–2.65(m,1H,CH2),2.37(s,3H,CH3),2.16(s,3H,Ad–H),2.10(s,6H,Ad–H),1.63(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:190.3,166.3,164.0,145.9,138.3,132.6,130.7,129.4,127.6,123.8,114.8,113.6,102.7(SeCN),84.8,70.2,65.6,40.8,35.9,35.3,30.8,28.5,21.2ppm.IR(KBr):2912,2852,2152(SeCN),1720,1666,1597cm–1。HRMS(ESI)m/z计算值C30H31NNaO4Se for[M+Na]+572.1311,实验值572.1318。旋光值:[α]25 D=–12.7(c 0.63,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tR(次峰)=17.7min,tS(主峰)=19.6min。
实施例23
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入5-烯丙氧基-β-四氢萘酮金刚烷酯(19mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-5-烯丙氧基-β-四氢萘酮金刚烷酯(24mg,产率98%,71%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-5-烯丙氧基-β-四氢萘酮金刚烷酯的相关表征结果如下:1H NMR(400MHz,CDCl3)δ:7.60(dd,J=7.6,0.8Hz,1H,Ar–H),7.30(t,J=8.0Hz,1H,Ar–H),7.07(d,J=8.0Hz,1H,Ar–H),6.11–6.01(m,1H,CH2CH),5.43(dd,J=17.2,1.2Hz,1H,CH2CH),5.33(dd,J=10.8,1.2Hz,1H,CH2CH),4.64–4.54(m,2H,OCH2),3.30–3.19(m,2H,CH2),2.89–2.80(m,1H,CH2),2.68–2.60(m,1H,CH2),2.15(s,3H,Ad–H),2.08(s,6H,Ad–H),1.62(s,6H,Ad–H)。13C{1H}NMR(100MHz,CDCl3)δ:192.1,166.0,155.7,132.6,132.4,131.4,127.7,119.5,117.8,116.8,102.4(SeCN),84.8,69.1,65.8,40.7,35.9,34.4,30.8,22.3ppm.IR(KBr):2914,2854,2154(SeCN),1712,1668,1581,1467cm–1。HRMS(ESI)m/z计算值C25H28NO4Se for[M+H]+486.1178,实验值486.1189。旋光值:[α]25 D=–26.2(c 0.57,CH2Cl2)。高效液相色谱(HPLC):AD-H柱(正己烷/异丙醇95:5,v/v,1.0mL min–1,254nm),tR(次峰)=9.5min,tS(主峰)=10.5min。
实施例24
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入7-甲氧基-β-四氢萘酮甲酯(12mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-7-甲氧基-β-四氢萘酮甲酯(12mg,产率71%,13%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-7-甲氧基-β-四氢萘酮甲酯的相关表征结果如下:mp:141–143℃。1H NMR(400MHz,CDCl3)δ:7.46(d,J=2.4Hz,1H,Ar–H),7.17(s,1H,Ar–H),7.16(d,J=2.4Hz,1H,Ar–H),3.84(s,3H,OCH3),3.81(s,3H,CO2CH3),3.29–3.24(m,1H,CH2),3.14–2.97(m,2H,CH2),2.77–2.70(m,1H,CH2)。13C{1H}NMR(100MHz,CDCl3)δ:191.5,167.8,158.8,136.0,130.7,130.3,123.9,109.8,101.8(SeCN),64.2,55.6,53.9,35.3,27.2ppm.IR(KBr):2156(SeCN),1728,1666,1606,1498cm–1。HRMS(ESI)m/z计算值C14H14NO4Se for[M+H]+340.0083,实验值340.0089。旋光值:[α]25 D=+2.86(c 0.42,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tR(次峰)=19.8min,tS(主峰)=18.2min。
实施例25
氩气条件下将三氟甲磺酸镍(1.8mg,0.005mmol)和4,6-双((R)-4-苯基-4,5-二氢噁唑)二苯并呋喃(2.3mg,0.005mmol)溶于二氯甲烷(1.0mL),室温下搅拌30分钟,随后加入β-四氢萘酮异丁酯(13mg,0.05mmol)和氮-硒氰基糖精(18mg,0.06mmol),-78℃下搅拌反应12小时后,减压旋转蒸发除去溶剂,残留物经快速硅胶柱纯化,得到(S)-2-硒氰基-β-四氢萘酮异丁酯(14mg,产率80%,45%ee),其纯度经氢谱鉴定大于95%。
本实施例所制备的(S)-2-硒氰基-β-四氢萘酮异丁酯的相关表征结果如下:1HNMR(400MHz,CDCl3)δ:8.02(d,J=8.0Hz,1H,Ar–H),7.57(t,J=7.6Hz,1H,Ar–H),7.37(t,J=7.6Hz,1H,Ar–H),7.27(d,J=7.6Hz,1H,Ar–H),4.03–3.94(m,2H,CO2CH2),3.30–3.04(m,3H,CH2),2.79–2.72(m,1H,CH2),1.95–1.85(m,1H,CH),0.81(dd,J=6.8,3.2Hz,6H,CH3)。13C{1H}NMR(100MHz,CDCl3)δ:191.6,167.3,143.2,135.1,130.2,129.0,128.2,127.4,101.9(SeCN),72.9,64.4,34.9,27.9,27.6,18.7ppm.IR(KBr):2962,2927,2154(SeCN),1728,1678,1629,1598cm–1。HRMS(ESI)m/z计算值C16H18NO3Se for[M+H]+352.0446,实验值352.0442。旋光值:[α]25 D=+4.31(c 0.51,CH2Cl2)。高效液相色谱(HPLC):OD-H柱(正己烷/异丙醇90:10,v/v,1.0mL min–1,254nm),tR(次峰)=11.1min,tS(主峰)=11.9min。
综上所述,以上仅为本发明的较佳实施例而已,并非用于限定本发明的保护范围。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (8)
2.根据权利要求1所述的硒氰基化试剂的应用,其特征在于:有机溶剂Ⅲ选用不与氮-硒氰基糖精、β-酮酯类化合物Ⅱ以及催化剂反应的腈类溶剂或卤代烃类溶剂;氮-硒氰基糖精在有机溶剂Ⅲ中的浓度为1 mg/mL~50 mg/mL,氮-硒氰基糖精与β-酮酯类化合物Ⅱ的摩尔比为1~3:1;催化剂中金属路易斯酸与β-酮酯类化合物Ⅱ的摩尔比值为0.1~1.0:1,催化剂中手性氮配体与β-酮酯类化合物Ⅱ的摩尔比值为0.1~1.0:1。
3.根据权利要求1所述的硒氰基化试剂的应用,其特征在于:R1为氢、卤素、苯基、萘基、四氢萘基、联苯基、烯丙基烷氧基、苄基烷氧基或烷基,R2为甲基、叔丁基或金刚烷基;有机溶剂Ⅲ为乙腈、二氯甲烷或三氯甲烷;氮-硒氰基糖精在有机溶剂Ⅲ中的浓度为10 mg/mL~30 mg/mL,氮-硒氰基糖精与β-酮酯类化合物Ⅱ的摩尔比为1~1.3:1;催化剂中金属路易斯酸与β-酮酯类化合物Ⅱ的摩尔比值为0.1~0.2:1,催化剂中手性氮配体与β-酮酯类化合物Ⅱ的摩尔比值为0.1~0.2:1;制备具有手性的含硒氰基化合物的反应温度为-40 0C~-80 0C。
4.根据权利要求1所述的硒氰基化试剂的应用,其特征在于:镍盐为三氟甲磺酸镍,铜盐为三氟甲磺酸铜,手性噁唑啉配体为手性4,6-双(4,5-二氢噁唑)-二苯并呋喃类配体。
7.根据权利要求6所述的硒氰基化试剂的应用,其特征在于:有机溶剂Ⅰ选用不与氮-卤代糖精以及硒氰酸银发生反应的腈类溶剂或卤代烃类溶剂;有机溶剂Ⅰ与氮-卤代糖精的体积质量比为1 mL/g~100 mL/g,硒氰酸银与氮-卤代糖精的摩尔比为1~5:1。
8.根据权利要求6所述的硒氰基化试剂的应用,其特征在于:有机溶剂Ⅰ为乙腈、二氯甲烷或三氯甲烷;有机溶剂Ⅰ与氮-卤代糖精的体积质量比为1 mL/g~50 mL/g,硒氰酸银与氮-卤代糖精的摩尔比为1~2:1。
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